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No use, distribution or reproduction is permitted which does not comply with these terms. Human malignant melanoma is a highly aggressive, heterogeneous and drug-resistant cancer. Due to a high number of clones, harboring various mutations that affect key pathways, there is an exceptional level of phenotypic variation and intratumor heterogeneity ITH in melanoma. This poses a significant challenge to personalized cancer medicine.
Hitherto, it remains unclear to what extent the heterogeneity of melanoma affects the immune microenvironment. Herein, we explore the interaction between the tumor heterogeneity and the host immune response in a melanoma cohort utilizing The Cancer Genome Atlas TCGA. The Overall Survival OS among groups was analyzed using Kaplan—Meier curves with the log-rank test and multivariate cox regression.
RNA-seq data were evaluated to identify differentially expressed immunomodulatory genes. The reverse phase protein array RPPA data platform was used to validate immune responses at protein level. Highly heterogeneous melanoma tumors are associated with reduced immune cell infiltration and immune response activation as well as decreased survival. Our results reveal that intratumor heterogeneity is an indicative factor for patient survival due to its impact on anti-tumor immune response.
Keywords: immunomodulator, intratumor heterogeneity, The Cancer Genome Atlas, tumor infiltrating lymphocytes, melanoma. Melanoma is a highly heterogeneous disease with genetic and phenotypic diversity 1. The coexistence of cells with different phenotypic and molecular features within one tumor is named intratumor heterogeneity ITH 2.
